An Open Label, Multicenter, Phase 1/2 Study to Explore the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of TRX-221 in the Treatment of Patients With EGFR Mutant NSCLC Who Progressed Following Prior Therapy With EGFR TKI

Plain English Summary

A Study to Investigate Safety, Tolerability, PK and Anti-tumor Activity of TRX-221 in EGFRm NSCLC Patients is a Phase 2 clinical trial sponsored by Therapex Co., Ltd studying Carcinoma, Non-Small-Cell Lung, EGFR Mutant Advanced Non-Small Cell Lung Cancer. This study tested the safety and effectiveness of a new drug called TRX-221 in patients with a specific type of lung cancer. It was for adults with non-small cell lung cancer (NSCLC) that had spread and did not respond to previous treatments targeting EGFR mutations. Participation involved taking TRX-221 orally, with regular check-ups to monitor for side effects and tumor response. Due to the trial's termination, there are no direct alternatives from this specific study, but standard treatments for advanced NSCLC remain an option. The trial aims to enroll 19 participants.

Official Summary

This is a Phase 1/2, open-label study designed to investigate the safety, tolerability, PK, and anti-tumor activity of the study treatment in the treatment of patients with EGFR mutant NSCLC, who progressed following prior standard treatments which include the approved EGFR-TKIs with activity against T790M (e.g., osimertinib).

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with non-small cell lung cancer (NSCLC) that has spread and has specific EGFR mutations. Patients whose cancer has not responded to at least one prior EGFR-targeted therapy (like osimertinib). Individuals with a good general health status (ECOG 0 or 1) and adequate organ function. Patients with certain specific EGFR resistance mutations (C797X) were prioritized in Phase 2. This trial is studying Carcinoma, Non-Small-Cell Lung, EGFR Mutant Advanced Non-Small Cell Lung Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measured how safe and tolerable TRX-221 was, and whether it could shrink tumors or stop their growth in patients with specific EGFR mutations that no longer respond to standard dr The specific primary outcome measures are: [Phase1 PartA: Dose Escalation] To assess the safety/tolerability and determine the MTD/RP2D range of TRX-221 (Approx. 12 months); [Phase1 PartB: Dose Exploration] To determine the RP2D of TRX-221 (Approx. 6-12 months); [Phase2] To assess the anti-tumor activity of TRX-221 in patients with the selected EGFR-resistant mutation type (Approx. 6-12 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aimed to address a critical need for new treatments in patients with EGFR-mutated NSCLC who have developed resistance to existing therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Carcinoma, Non-Small-Cell Lung, EGFR Mutant Advanced Non-Small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

The termination of this Phase 1/2 trial suggests potential safety or efficacy concerns, impacting the investment outlook for TRX-221 in the competitive EGFR-mutated NSCLC market. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if TRX-221 was being investigated for your specific type of lung cancer and if there were any available alternatives. Participation would have involved taking the study drug at home and visiting study centers for regular tests, scans, and doctor's appointments. Be prepared for frequent monitoring of your health and potential side effects throughout the study. The trial is being conducted at 6 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 19 participants

Interventions

• DRUG: TRX-221 — TRX-221 oral dose as defined

Primary Outcomes

• [Phase1 PartA: Dose Escalation] To assess the safety/tolerability and determine the MTD/RP2D range of TRX-221 (Approx. 12 months)
• [Phase1 PartB: Dose Exploration] To determine the RP2D of TRX-221 (Approx. 6-12 months)
• [Phase2] To assess the anti-tumor activity of TRX-221 in patients with the selected EGFR-resistant mutation type (Approx. 6-12 months)

Secondary Outcomes

• To characterize the PK profile of the study treatment (Throughout the study period, an average of 1 year)
• To evaluate the preliminary anti-tumor activity of the study treatment (Phase 1) (Approx. 12 months)
• To evaluate additional anti-tumor activity of the study treatment other than the primary endpoint (Phase 2) (Approx. 12 months)
• To assess the safety and tolerability of the study treatment (Phase 2) (Approx. 12 months)

Full Eligibility Criteria

Inclusion Criteria:

1. Patients with ECOG performance status score of 0 or 1
2. Histologically or cytologically confirmed diagnosis of relapsed or refractory, locally unresectable advanced or metastatic NSCLC harboring an activating EGFR mutation
3. Failed standard of care treatments progressed after anti tumor treatments including at least 1 approved EGFR TKI \[Phase2: TKIs should include the approved EGFR TKIs with activity against T790M (e.g., osimertinib)\]
4. Slots may be reserved for patients with certain resistant mutations (i.e., EGFR C797X mutation with or without T790M mutation as required by the sponsor) \[Phase 1\]
5. EGFR C797X mutation with or without T790M mutation \[Phase 2\]
6. Not received more than 1 prior line of platinum based chemotherapy in the metastatic setting \[Phase 2\]
7. Having at least 1 measurable tumor lesion per RECIST v1.1 criteria \[Phase 2\]
8. Having adequate bone marrow, hepatic, and renal function as specified in the protocol

Exclusion Criteria:

1. NSCLC with mixed cell histology or a tumor with histologic transformation of small cell elements
2. Patients having tumor with any additional known driver of alterations
3. Patients with presence of another active primary malignant tumor that has been diagnosed or required therapy within 2 years prior to the initiation of the study treatment
4. Patients who have unstable and symptomatic primary CNS tumors/metastasis, leptomeningeal metastases or spinal cord compression which are not suitable for enrollment, as judged by the Investigator
5. Patients having clinically active ongoing ILD of any etiology
6. Clinically significant cardiac conditions, infections, refractory GI diseases as specified in the protocol
7. Patients having any unresolved toxicities from prior anti tumor therapy and surgery greater than CTCAE Grade 1 at the time of starting the study treatment
8. Recent anticancer therapy: EGFR-TKI, Immunotherapy or any other systemic anticancer therapy or radiotherapy (specific duration prior to starting study medication per protocol)

Trial Locations

• Seoul National University Bundang Hospital, Seongnam, Kyeongki, South Korea
• The Catholic University of Korea St. Vincent Hospital, Suwon, Kyeongki, South Korea
• Chungbuk National University Hospital, Chungju, North Chungcheong, South Korea
• Severance Hospital, Seoul, South Korea
• Asan Medical Center, Seoul, South Korea
• Samsung Medical Center, Seoul, South Korea

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• EGFR-Mutated Lung Cancer
• Tyrosine Kinase Inhibitor Resistance
• Advanced Lung Cancer
• Metastatic Lung Cancer
• Oncology
• Thoracic Oncology
• Cancer Treatment
• Personalized Medicine

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